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CLINICAL SCENARIO

The patient is a 65 year old male with a long history


of type 2 diabetes and obesity. Otherwise his medical
history is unremarkable. He does not smoke. He had
knee surgery 10 years ago but otherwise has had no
other major medical problems. Over the years he has
tried numerous diets and exercise programs to reduce
his weight but has not been very successful. His
granddaughter just started high school and he wants
to see her graduate and go on to college. He
understands that his diabetes puts him at a high risk
for heart disease and is frustrated that he cannot lose
the necessary weight. His neighbor told him about a
colleague at work who had his stomach stapled and
as a result not only lost over 100 lbs. but also "cured"
his diabetes. He wants to know if this procedure
P.I.C.O

P= Patient Problem:
How would you describe a group of patients
similar to yours? What are the most important
characteristics of the patient? This may include the
primary problem, disease, or co-existing
conditions. Sometimes the gender, age or race of a
patient might be relevant to the diagnosis or
treatment of a disease.
I= Intervention, prognostic factor or exposure:
Which main intervention, prognostic factor, or
exposure are you considering? What do you want
to do for the patient? Prescribe a drug? Order a
test? Order surgery? Or what factor may influence
the prognosis of the patient - age, co-existing
problems, or previous exposure?
C= Comparison:
What is the main alternative to compare with the
intervention? Are you trying to decide between
two drugs, a drug and no medication or placebo,
or two diagnostic tests? Your clinical question
may not always have a specific comparison.
O= Outcome:
What can you hope to accomplish, measure,
improve or affect? What are you trying to do for
the patient? Relieve or eliminate the symptoms?
Reduce the number of adverse events? Improve
function or test scores?
P.I.C.O TABLE

OUR CASE
Patient
obese, diabetes type 2, male
Problem
Intervention stomach stapling (gastric bypass surgery;
bariatric surgery)
Comparison standard medical care
Outcome remission of diabetes; weight loss;
mortality
CLINICAL QUESTION
For our patient, the clinical question might be: In
patients with type 2 diabetes and obesity, is
bariatric surgery more effective than standard
medical therapy at increasing the probability of
remission of diabetes?
Two additional elements of the well-built clinical
question are the type of question and the type of
study. This information can be helpful in focusing
the question and determining the most
appropriate type of evidence or study.
The type of question is important and can help
lead you to the best study design:

Most common type of


Type of study:
questions:
Diagnosis how to select and prospective, blind comparisonto a gold standard or cross-
interpret diagnostic tests sectional
Therapyhow to select
treatments that do more good
than harm and that are worth randomized controlled trial > cohort study
the efforts and costs of using
them
Prognosishow to estimate the
patient’s likely clinical course
over time (based on factors
cohort study > case control > case series
other than the intervention)
and anticipate likely
complications of disease
Harm/Etiologyhow to identify
causes for disease (including cohort > case control > case series
iatrogenic forms)
STUDY DESIGN
Case series and Case reports consist of collections of
reports on the treatment of individual patients or a
report on a single patient. Because they are reports of
cases and use no control groups to compare outcomes,
they have little statistical validity.

Case control studies are studies in which patients who


already have a specific condition are compared with
people who do not have the condition. The researcher
looks back to identify factors or exposures that might
be associated with the illness. They often rely on
medical records and patient recall for data collection.
These types of studies are often less reliable than
randomized controlled trials and cohort studies
because showing a statistical relationship does not
mean than one factor necessarily caused the other.
Cohort studies identify a group of patients who are
already taking a particular treatment or have an
exposure, follow them forward over time, and then
compare their outcomes with a similar group that has
not been affected by the treatment or exposure being
studied. Cohort studies are observational and not as
reliable as randomized controlled studies, since the
two groups may differ in ways other than in the
variable under study.

Randomized controlled clinical trials are carefully


planned experiments that introduce a treatment or
exposure to study its effect on real patients. They
include methodologies that reduce the potential for
bias (randomization and blinding) and that allow for
comparison between intervention groups and control
(no intervention) groups. A randomized controlled trial
is a planned experiment and can provide sound
evidence of cause and effect.
Systematic Reviews focus on a clinical topic
and answer a specific question. An extensive
literature search is conducted to identify
studies with sound methodology. The studies
are reviewed, assessed for quality, and the
results summarized according to the
predetermined criteria of the review question.

A Meta-analysis will thoroughly examine a


number of valid studies on a topic and
mathematically combine the results using
accepted statistical methodology to report the
results as if it were one large study.
Cross-sectional studies describe the relationship between
diseases and other factors at one point in time in a defined
population. Cross sectional studies lack any information on
timing of exposure and outcome relationships and include
only prevalent cases. They are often used for comparing
diagnostic tests. Studies that show the efficacy of a
diagnostic test are also called prospective, blind
comparison to a gold standard study. This is a controlled
trial that looks at patients with varying degrees of an
illness and administers both diagnostic tests — the test
under investigation and the “gold standard” test — to all of
the patients in the study group. The sensitivity and
specificity of the new test are compared to that of the gold
standard to determine potential usefulness.
Qualitative Research answers a wide variety of
questions related to human responses to actual or
potential health problems.The purpose of
qualitative research is to describe, explore and
explain the health-related phenomena being
studied.

Retrospective cohort (or historical cohort) follows


the same direction of inquiry as a cohort study.
Subjects begin with the presence or absence of an
exposure or risk factor and are followed until the
outcome of interest is observed. However, this
study design uses information that has been
collected in the past and kept in files or
databases. Patients are identified for exposure or
non-exposures and the data is followed forward
For our patient, the clinical question
is:
In patients with type 2 diabetes and
obesity, is bariatric surgery more
effective than standard medical
therapy at increasing the probability
of remission of diabetes?

It is a therapy question and the best


evidence would be a randomized
controlled trial (RCT). If we found
numerous RCTs, then we might want
to look for a systematic review.
PICO ANDS SEARCH STRATEGY
PICO Clinical Question Search Strategy
Patient / obese, diabetes type 2,
diabetes type 2, obesity
Problem male
stomach stapling (gastric
Intervention bypass surgery; bariatric bariatric surgery
surgery)
Comparison
standard medical care
(if any)
remission of diabetes;
Outcome
weight loss; mortality
Type of
therapy (see below)
Question
Clinical Query – Therapy/narrowor
Type of
RCT Limit to randomized controlled
Study
trial as publication type
Selecting the Resources
Evidence-Based Practice requires that clinicians search the literature to
find answers to their clinical questions. There are literally millions of
published reports, journal articles, correspondence and studies available
to clinicians. Choosing the best resource to search is an important
decision. Large databases such as PubMed/MEDLINE will give you
access to the primary literature. Secondary resources such as ACP
Journal Club, Essential Evidence, FPIN Clinical Inquiries, and Clinical
Evidence will provide you with an assessment of the original study. The
Cochrane Library provides access to systematic reviews which help
summarize the results from a number of studies. These are often called
“pre-appraised” or EBP resources.
To quickly find an answer, we might first look at an appraised resource,
such as ACP Journal Club. ACP Journal Club’s general purpose is to
select from the biomedical literature articles that report original studies
and systematic reviews that warrant immediate attention by physicians
attempting to keep pace with important advances in internal medicine.
These articles are summarized in value-added abstracts and commented
on by clinical experts. Studies included in this small database are
relevant, newsworthy and critically appraised for study methodology.
EBP Resources:
ACP Journal Club
This Web site comprises a 10-year archive of the cumulative electronic contents
of "ACP Journal Club", with recurrent weeding of out-of-date articles. The content
is carefully selected from over 100 clinical journals through reliable application of
explicit criteria for scientific merit, followed by assessment of relevance to
medical practice by clinical specialists.
Clinical Evidence
Clinical Evidence describes the best available evidence from systematic reviews,
RCTs, and observational studies when appropriate for assessing the benefits and
harms of treatments.
Dynamed
Dynamed is a point-of-care reference resource designed to provide clinicians with
current, evidence-based information to support clinical decision-making.
Essential Evidence
Essential Evidence is a one-stop reference that includes evidence-based answers
to clinical questions concerning symptoms, diseases, and treatment.
FPIN Clinical Inquiries
Clinical Inquiries provides answers to clinical questions by using a structured
search, critical appraisal, clinical perspective, and rigorous peer review. FPIN
Clinical Inquiries deliver evidence for point of care use.
UpToDate
UpToDate is an evidence-based, peer reviewed information resource available via
the Web, desktop/laptop computer, and PDA/mobile device
Article Databases:
 PubMed (MEDLINE)
PubMed comprises more than 22 million citations for biomedical articles
from MEDLINE and life science journals. Access to titles / abstracts is
free. Citations may include links to full-text articles from PubMed Central
or publisher web sites.
 Cochrane Library.
The Cochrane Library contains high-quality, independent evidence to
inform healthcare decision-making. It includes reliable evidence from
Cochrane systematic reviews and a registry of published clinical trials.
The methodology used to create the Cochrane reviews is recognized as
the gold standard for developing systematic reviews.
 Center for Reviews and Dissemination (DARE).
The databases DARE, NHS, EED and HTA assist decision-makers by
identifying and describing systematic reviews and economic
evaluations, appraising their quality, and highlighting their relative
strengths and weaknesses.
E-Books and Libraries:

Access Medicine - CANCELLED June 2015
Access to medical titles with information for completing evaluations, diagnoses,
case management decisions, research pursuits, medical education, self-
assessment, and board reviews.
more...
ACP Smart Medicine
Formerly known as ACP PIER, ACP Smart Medicine is an online clinical tool that
provides evidence-based clinical guidance to improve clinical care. It is free to
ACP members or can be purchased as a subscription.

ClinicalKey
Online search tool for e-books, journals, Procedures Consult, First Consult,
surgical Vitals and other clinical information.Please note: This database replaces
MD Consult.To access PDF files for E-books, you must register for and login to a
personal account. Click here to create a FREE user profile. If you get a session
time out message while searching ClinicalKey, please close or refresh your
browser and try your search again.

Scientific American Surgery
Scientific American Surgery, formerly ACS Surgery, contains
authoritative recommendations on current surgical care from
master surgeons. Includes drawings, graphs, photos, and
decision-making algorithms. Please note: This resource has a
limited number of simultaneous users. Try again later if unable to
access..

Stat!Ref
An online collection of electronic books. Additional resources are
also available from the "Tools & Features" menu including
Stedman's Medical Dictionary, MedCalc 3000, and nursing
podcasts (NCLEX-RN exam). Please note: This resource has a
limited number of simultaneous users. Try again later if unable to
access.
Meta / Cross Search Engines:
 TRIP (Turning Research into Practice)
The TRIP Database searches across multiple internet sites for evidence-
based content. It covers key medical journals, Cochrane Systematic
reviews, clinical guidelines, and other highly relevant websites to help
health professionals find high quality clinical evidence for clinical
practice.

Step 1: Use PICO to formulate the search strategy; start with


the Patient problem(s) and Intervention

Enter the term for the patient problem and the intervention:
obesity AND diabetes type 2 AND bariatric surgery. PubMed
attempts to map your terms to appropriate Medical Subject
Headings (MeSH). MeSH is the standard terminology used by
the indexer and helps find articles on specific topics,
regardless of the exact wording used by the authors.
Step 2. Look at Search Details to verify MeSH
terms
Look in the Search Details box (lower right
column; click on "See more" to expand) to see
the terms that PubMed actually used in its
search. You want to be sure PubMed found the
appropriate MeSH terms. PubMed will
automatically also search for your terms as
words in the title and abstract. Obesity is a
MeSH term, diabetes type 2 is translated to the
MeSH term of diabetes mellitus, type 2, and
bariatric surgery is a MeSH term. If your
search did not find the appropriate MeSH
Step 3. Limit to appropriate study design
This is a therapy question. We know from the previous discussion
that the best evidence for a therapy question is a randomized
controlled clinical trial (RCT). Use the Filters column from the main
results page to limit to Randomized Controlled Trial as an article
type. You may need to click on "more" to see additional filters if
RCT is not listed.
You can also use the Clinical Queries function to limit the results to
study methodologies relevant to therapy questions. Copy your last
search strategy obesity AND diabetes type 2 AND bariatric surgery.
Click on Advanced under the search box; then click on More
Resources near the top of the page; then select Clinical Queries.
Paste the search strategy in the Clinical Query search box and hit
Search. The first column of results is Clinical Study Categories.
Select the type of question (Therapy) and the type of search
(Narrow). You may get more search results using the Clinical
Queries function.
Step 4. Review the results
Both methods limit your results to RCTs. The fourth citation is the
Mingrone article that we found in ACP Journal Club.
Step 1: Use PICO to formulate the search strategy; start with the Patient
problem(s) and Intervention
Step 2. Look at Search Details to verify MeSH
terms
Step 3. Limit to appropriate study design
Evaluating the Validity of a Therapy Study

We have now identified current information which can


answer our clinical question. The next step is to read
the article and evaluate the study. There are three
basic questions that need to be answered for every
type of study:
 Are the results of the study valid?
 What are the results?
 Will the results help in caring for my patient?
This tutorial will focus on the first question: are the
results of the study valid? The issue of validity speaks
to the "truthfulness" of the information. The validity
criteria should be applied before an extensive analysis
of the study data. If the study is not valid, the data may
Read the following article and determine if it meets the validity
criteria.
Mingrone G. Bariatric surgery versus conventional
medical therapy for type 2 diabetes. N Engl J Med.
2012 Apr 26;366(17):1577-85. doi:
10.1056/NEJMoa1200111. Epub 2012 Mar 26.
PubMed PMID:22449317.

1. Were patients randomized?


The assignment of patients to either group
(treatment or control) must be done by a random
allocation. This might include a coin toss (heads to
treatment/tails to control) or use of randomization
tables, often computer generated. Research has
shown that random allocation comes closest to
insuring the creation of groups of patients who will
be similar in their risk of the events you
2. Was group allocation concealed?

The randomization sequence should be concealed from


the clinicians and researchers of the study to further
eliminate conscious or unconscious selection bias.
Concealment (part of the enrollment process) ensures
that the researchers cannot predict or change the
assignments of patients to treatment groups. If
allocation is not concealed it may be possible to
influence the outcome (consciously or unconsciously) by
changing the enrollment order or the order of treatment
which has been randomly assigned. Concealed allocation
can be done by using a remote call center for enrolling
patients or the use of opaque envelopes with
assignments. This is different from blinding which
happens AFTER randomization.
3. Were patients in the study groups
similar with respect to known prognostic
variables?

The treatment and the control group


should be similar for all prognostic
characteristics except whether or not they
received the experimental treatment. This
information is usually displayed in Table
which outlines the baseline
characteristics of both groups. This is a
good way to verify that randomization
resulted in similar groups.
4. To what extent was the study blinded?

Blinding means that the people involved in the study


do not know which treatments were given to which
patients. Patients, researchers, data collectors and
others involved in the study should not know which
treatment is being administered. This helps eliminate
assessment bias and preconceived notions as to how
the treatments should be working. When it is difficult
or even unethical to blind patients to a treatment,
such as a surgical procedure, then a "blinded"
clinician or researcher is needed to interpret the
results.
5. Was follow-up complete?

The study should begin and end with the same number
of patients in each group. Patients lost to the study
must be accounted for or risk making the conclusions
invalid. Patients may drop out because of the adverse
effects of the therapy being tested. If not accounted for,
this can lead to conclusions that may be overly
confident in the efficacy of the therapy. Good studies
will have better than 80% follow-up for their patients.
When there is a large loss to follow-up, the lost patients
should be assigned to the "worst-case" outcomes and
the results recalculated. If these results still support the
original conclusion of the study then the loss may be
acceptable.
6. Were patients analyzed in the groups to which
they were first allocated?

Anything that happens after randomization can affect the


chances that a patient in a study has an event. Patients
who forget or refuse their treatment should not be
eliminated from the study results or allowed to “change
groups”. Excluding noncompliant patients from a study
group may leave only those that may be more likely to
have a positive outcome, thus compromising the
unbiased comparison that we got from the process of
randomization. Therefore all patients must be analyzed
within their assigned group. Randomization must be
preserved. This is called "intention to treat" analysis.
7. Aside from the experimental
intervention, were the groups
treated
equally?
Both groups must be treated the
same except for administration of the
experimental treatment. If
"cointerventions" (interventions
other than the study treatment which
are applied differently to both
groups) exist they must be described
in the methods section of the study.\
What are the results?

How large was the treatment effect? What was the


absolute risk reduction?
Results: At 2 years, diabetes remission had
occurred in none of the patients receiving medical
therapy, as compared with 15 of 20 (75%)
undergoing gastric bypass and 19 of 20 (95%)
undergoing biliopancreatic diversion (P<0.001 for
both comparisons). There was a significant
association between study group and rate of
remission. However, since there were no
remissions in the medical-therapy group, risk ratios
were computed in a more conservative fashion on
the assumption that remission had occurred in the
2 patients in the medical-therapy group who
dropped out.
CONTINGENCY TABLE

Treatment Remission No remission of Total


of Diabetes Diabetes
Gastric 20
15 5
Bypass
Medical 20
2 18
Therapy
Experimental Event Rate (EER) = 15 / 20 = 75%
outcome present / total in experimental group
Control Event Rate (CER) = 2 / 20 = 10%
outcome
present / total in control group
Absolute Benefit Increase (ABI) = 75% - 10% =
65%
is the arithmetic difference between the rates of
events in the experimental and control group.
Absolute Benefit Increase (ABI) refers to the
increase of a good event as a result of the
intervention.
An Absolute Risk Reduction (ARR) refers to the
decrease of a bed event as the result of the
intervention. [ARR = EER-CER]
Relative Risk (RR) = .75 / .10 = 7.5 is the ratio of
the risk in the experimental group compared to the
risk in the control group.
proportional reduction in risk between the
rates of events in the control group and the
experimental group. [RR = EER/CER]
Relative Benefit Increase (RBI) = 65% / 10%
= 650% is the proportional increase in benefit
between the rates of events in the control
group and the experimental group. [RBI = EER
- CER / CER]
Numbers Needed to Treat (NNT) = 1 /
.65 = 2 is the number of patients who
need to be treated to prevent one bad
outcome or produce one good
outcome. In other words, it is the
number of patients that a clinician
would have to treat with the
experimental treatment compared to
the control treatment to achieve one
additional patient with a favorable
outcome. [NNT = 1/ARR]
Clinical versus Statistical Significance

1. Although it is tempting to equate statistical


significance with clinical importance, critical readers
should avoid this temptation.
2. To be clinically important requires a substantial
change in an outcome that matters.
3. Statistically significant changes, however, can be
observed with trivial outcomes.
4. And because statistical significance is powerfully
influenced by the number of observations, statistically
significant changes can be observed with trivial (small)
changes in important outcomes.
5. Large studies can be significant without being
clinically important and small studies may be important
without being significant." (Effective Clinical Practice,
July/August 2001, ACP)
1. Clinical significance has little to do with statistics and
is a matter of judgment.
2. Clinical significance often depends on the magnitude
of the effect being studied. It answers the question "Is the
difference between groups large enough to be worth
achieving?"
3. Studies can be statistically significant yet clinically
insignificant. For example, a large study might find that a
new antihypertensive drug lowered BP, on average, 1 mm Hg
more than conventional treatments. The results were
statistically significant with a P Value of less than .05
because the study was large enough to detect a very small
difference. However, most clinicians would not find the 1 mm
Hg difference in blood pressure large enough to justify
changing to a new drug. This would be a case where the
results were statistically significant (p value less than .05)